1. Field of the Invention
The present invention relates generally to advancements in medical treatment. More specifically, this present invention is related to effectively treating a target region of tissue with Irreversible Electroporation (IRE), followed by introduction of regenerative materials leading to regrowth, restructuring, and cellular repopulation of the treated region.
2. Description of the Related Art
Tissue ablation is a medically necessary activity with destructive effects leading to cellular death within a target region (also herein called target tissue). Historically this endeavor has included a series of methods, each with varying degrees of effectiveness and subsequent levels of unintended consequences including adverse effects to surrounding tissue. Depending on the method used for tissue ablation and any underlying pathophysiology related to the medical treatment, the patient may have remaining tissue that is damaged, disorganized, and in need of repair. This is due to the fact that ablation techniques used historically have been nonselective in that they mediate cell death with methods such as extreme heat or cold. These methods will non-selectively and adversely affect blood vessels, nerves, and connective structures adjacent to the ablation zone. Disruption of the nerves locally impedes the body's natural ability to sense and regulate homeostatic and repair processes at and surrounding the ablation region. Disruption of the blood vessels prevents removal of debris and detritus. This also prevents or impedes repair systems, prevents homing of immune system components, and generally prevents normal blood flow that could carry factors such as hormones to the area. Without the advantage of a steady introduction of new materials to a damaged area, reconstruction of the blood vessels and internal linings become retarded as redeployment of cellular materials is inefficient or even impossible. Therefore historical ablation treatments do not leave tissue in an optimal state for self-repair in regenerating the region.
Recent developments offer an opportunity to advance the regenerative process following ablation treatments. A recent development in tissue ablation involves the use of irreversible electroporation (IRE). IRE offers the advantage of being a nonthermal ablation technique, which avoids some of the adverse consequences associated with temperature changes of ablative techniques such as radiofrequency (RF) ablation, microwave ablation, or even cryoablation. In addition, IRE has been shown to have sparing effects on structural components, leaving blood vessels and connective structures intact. This provides the advantage of providing a scaffold system which could then be utilized to increase the rate of reconstruction in the rebuilding process of recovery following ablation.
IRE has been applied to the treatment of tissue using ablation, and this technology has the distinct advantage of inducing cell necrosis without raising the temperature of the ablation zone. More specifically IRE is a technology where electrical pulses in the range of nanoseconds to milliseconds are applied to tissue to produce cellular necrosis and irreversible cell membrane permeabilization. More precisely, IRE treatment acts by creating defects in the cell membrane that are nanoscale in size and that lead to a disruption of homeostasis while sparing connective and scaffolding structure and tissue. These points have been addressed in the following publications, which are hereby incorporated by reference: Lavee J. A Novel Nonthermal Energy Source for Surgical Epicardial Atrial Ablation: Irreversible Electroporation. The Heart Surgery Forum. Vol. 10(2):96-101 (2007), and U.S. Patent Application Publication Number US 20060293731 A1, “Methods and systems for treating tumors using electroporation,” application Ser. No. 11/165,961 filed on Jun. 24, 2005.
A distinct advantage of the IRE technology is the sparing of surrounding tissue, and in fact the structure of surrounding bile ducts, blood vessels, and connective tissue remains intact following application of IRE. This technology has been described in the following two patent application publications which are hereby incorporated by reference: Patent Application Publication Number WO2005/06284A2, “Tissue Ablation with Irreversible Electroporation,” as well as U.S. Patent Application Publication Number US 2007/0043345A1, “Tissue Ablation with Irreversible Electroporation,” application Ser. No. 10/571,162.
By utilizing IRE in combination with advanced regenerative technologies, there exists a vast potential for regrowth, regeneration, and cellular repopulation in a treated region that far surpasses current treatment modalities. The reason for this starts with the fact that the IRE treatment leaves structures such as blood vessels and nerves intact and ends with the fact that there are technologies that can take advantage of that fact for increased regeneration capabilities. Specifically, the remaining vessels and connective tissues are structures that provide a scaffold that can be built upon. These vessels can also act as a conduit for new materials, while remaining nerves can act to assist monitoring and mediating of the local conditions. Meanwhile, the introduction of regenerative materials to these locations can take advantage of the remaining foundation to advance regeneration. One example of a component of regenerative materials that would work synergistically with the IRE technology would be stem cells.
Effective development and use of stem cells is also a relatively recent development and is an emerging branch of technology that offers vast potential for enhancing regenerative capacity for an organ or tissue. A stem cell can be defined as a cell capable of producing unaltered daughter cells continuously, and a cell that is also capable of producing daughter cells that have differentiated characteristics. In other words, stem cells producing progeny that are to have separate or distinguished fates will have undergone asymmetric division while those daughter cells having the same fate have undergone symmetric division.
These concepts have been described in the following two papers, hereby incorporated by reference:    Smith A., A Glossary for Stem Cell Biology. Nature Vol. 441(7097):1060-61 (2006).    Morrison S. J., Kimble J., Asymmetric and Symmetric Stem Cell Divisions in Development and Cancer, 441(7097) Nature 1068, 1068-74 (2006).
One advantage of utilizing stem cells in a regenerative process involves the ability of a small number of cells to repopulate an area since the dividing cells have less potential for exhaustion on division. In fact, there are a variety of stem cell categories, which can be grossly broken into totipotent, pluripotent, multipotent, and unipotent, which are indicated here with respective decreasing plasticity or potency. A second advantage of utilizing stem cells is that the cells can differentiate into one or more cell types depending on the milieu of factors in the host niche environment. The power of this capacity can potentially be utilized as an astounding regenerative tool of medicine that could combat tissue injury, lead to treatments for degenerative diseases, and the normal decline of aging. This concept has been addressed in the following two papers, hereby incorporated by reference:    Rando T. A. Stem Cells, Ageing and the Quest for Immortality. Nature. Vol. 441(7097):1080-1086 (2006).    Ioannidou E., Therapeutic modulation of growth factors and cytokines in regenerative medicine, 12(19) Current Pharmaceutical Design. Vol. 12(19):2397 (2006).
Stem cells could also be used for therapies for progressive blindness, neurological disorders including stroke, Parkinson's disease, and multiple sclerosis, and also holds potential for treatment of heart disease. This concept has been discussed in the following three papers, hereby incorporated by reference:    Lindvall O., Kokaia Z., Stem cells for the treatment of neurological disorders. Nature. Vol. 441(7097): 1094-1096 (2006).    Couzin J., A Shot of Bone Marrow Can Help the Heart. Science. Vol 313: 1715-1716 (2006).    Srivastava D., Ivey K. N., Potential of Stem-Cell-Based Therapies for Heart Disease. Nature. Vol. 441(7097): 1097-1099 (2006).
This invention allows for the combined use of nonthermal ablation of undesired tissue through IRE with the introduction of regenerative materials that will allow the regrowth of tissue following ablation. A need exists for an apparatus and method for accomplishing effective ablation followed by introduction of regenerative materials so as to increase the rate of regrowth, the rate of reconstruction, and cellular repopulation of a region following ablation. There is a need for a method and device that can ultimately decrease patient recovery times in a significant number of different treatment situations through more effective regeneration. The proposed method and apparatus matches these needs and allows for an increased opportunity for regrowth in tissues through the introduction of regenerative materials that may include stem cells. The proposed method and apparatus also provides for a treatment that can be used widely; in tissues that naturally regenerate (to enhance the effectiveness and rate of regeneration), in tissues without significant natural regenerative powers, and in those with pathophysiological factors that may otherwise impede regenerations.
Applicant(s) believe(s) that the material incorporated above is “non-essential” in accordance with 37 CFR 1.57, because it is referred to for purposes of indicating the background of the invention or illustrating the state of the art. However, if the Examiner believes that any of the above-incorporated material constitutes “essential material” within the meaning of 37 CFR 1.57(c)(1)-(3), applicant(s) will amend the specification to expressly recite the essential material that is incorporated by reference as allowed by the applicable rules.